Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

Infection with COVID-19 promotes the progression of pancreatic cancer through the PI3K-AKT signaling pathway.

OBJECTIVE: To investigate the effect of COVID-19 infection on pancreatic cancer. METHODS: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. RESULTS: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. CONCLUSION: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

Establishment of a prognostic model toward lung squamous cell carcinoma based on m7G-related genes in the cancer genome atlas.

Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (m7G) modifications, a tRNA modification, are common in eubacteria, eukaryotes, and a few archaea. These modifications promote the turnover and stability of some mRNAs to prevent mRNA decay, improve translation efficiency, and reduce ribosomal pausing but are associated with poor survival in human cancer cells. However, expression of m7G-related genes in LUSC and their association with prognosis remain unclear. In the present study, we identified nine differentially expressed genes related to prognosis by comparing the expression profiles of tumor tissues (502 LUSC reports) with normal tissues (49 adjacent nontumor lung tissue reports). The genes included six upregulated genes (KLK7, LCE3E, AREG, KLK6, ZBED2, and MAPK4) and three downregulated genes (ADH1C, NTS, and ERLIN2). Based on these nine genes, patients with LUSC were classified into low- and high-risk groups to analyze the trends in prognosis. We found that the nine m7G-related genes play important roles in immune regulation, hormone regulation, and drug sensitivity through pathways including antigen processing and presentation, adherent plaques, extracellular matrix receptor interactions, drug metabolism of cytochrome P-450, and metabolism of cytochrome P-450 to xenobiotics; the functions of these genes are likely accomplished in part by m6A modifications. The effect of m7G-related genes on the diagnosis and prognosis of LUSC was further indicated by population analysis.NEW & NOTEWORTHY Based on the differential expression of 7-methylguanosine (m7G) modification-associated genes between normal and lung squamous cell carcinoma (LUSC) tissues, and considering the performance of our m7G-related gene risk profiles as independent risk factors in predicting overall survival, we conclude that m7G modification is closely linked to the development of LUSC. In addition, this study offers a new genetic marker for predicting the prognosis of patients with LUSC and presents a crucial theoretical foundation for future investigations on the relationship between m7G modification-related genes, immunity, and drug sensitivity in LUSC.

Uncovering the key pharmacodynamic material basis and possible molecular mechanism of extract of Epimedium against liver cancer through a comprehensive investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver cancer is a worldwide malignant tumor, and currently lacks effective treatments. Clinical studies have shown that epimedium (YYH) has therapeutic effects on liver cancer, and some of its prenylflavonoids have demonstrated anti-liver cancer activity through multiple mechanisms. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of YYH. AIM OF THE STUDY: This study aimed to screen the anti-cancer material basis of YYH via integrating spectrum-effect analysis with serum pharmacochemistry, and explore the multi-target mechanisms of YYH against liver cancer by combining network pharmacology with metabolomics. MATERIALS AND METHODS: The anti-cancer effect of the extract of YYH (E-YYH) was first evaluated in mice with xenotransplantation H22 tumor cells burden and cultured hepatic cells. Then, the interaction between E-YYH compounds and the cytotoxic effects was revealed through spectrum-effect relationship analysis. And the cytotoxic effects of screened compounds were verified in hepatic cells. Next, UHPLC-Q-TOF-MS/MS was employed to identify the absorbed components of E-YYH in rat plasma to distinguish anti-cancer components. Subsequently, network pharmacology based on anti-cancer materials and metabolomics were used to discover the potential anti-tumor mechanisms of YYH. Key targets and biomarkers were identified and pathway enrichment analysis was performed. RESULTS: The anti-cancer effect of E-YYH was verified through in vitro and in vivo experiments. Six anti-cancer compounds in plasma (icariin, baohuoside Ⅰ, epimedin C, 2″-O-rhamnosyl icariside Ⅱ, epimedin B and sagittatoside B) were screened out by spectrum-effect analysis. Forty-five liver-cancer-related targets were connected with these compounds. Among these targets, PTGS2, TNF, NOS3 and PPARG were considered to be the potential key targets preliminarily verified by molecular docking. Meanwhile, PI3K/AKT signaling pathway and arachidonic acid metabolism were found to be associated with E-YYH's efficacy in network pharmacology and metabolomics analysis. CONCLUSIONS: Our research revealed the characteristics of multi-component, multi-target and multi-pathway mechanism of E-YYH. This study also provided an experimental basis and scientific evidence for the clinical application and rational development of YYH.

An updated patent review of histone deacetylase (HDAC) inhibitors in cancer (2020 - present).

INTRODUCTION: Histone deacetylase (HDAC) inhibitors have been considered as an attractive strategy to reverse aberrant epigenetic changes associated with cancer treatments. The use of HDAC inhibitors in various cancer types has continued to develop for decades, bringing several novel HDAC inhibitors successfully into clinical trials. The combination use of HDAC inhibitors with other agents have also been developed and have demonstrated superior efficacy compared to that of monotherapy in recent studies. Hence, development of new anticancer treatment and therapeutic regimen is necessary. AREAS COVERED: This review summarizes a comprehensive review of the patent literature from 2020 to 2022 including HDAC inhibitors and their use as anticancer agents (searched from European Patent Office, 2020-2022). The approved and developing HDAC inhibitors are described. It also provides perspectives on the challenges and future opportunities. EXPERT OPINION: Although hundreds of clinical trials of HDAC inhibitors are still going on, the application for HDAC inhibitors has been limited at present . Not only in the anticancer treatment, but also non-oncology disease therapies are being investigated eagerly. Recently, applications of HDAC inhibitors in non-oncology diseases have also been revealed and proceeded to clinical trials. New indications for HDAC inhibitors are needed urgently in the future.

The effect of SMAD4 on the prognosis and immune response in hypopharyngeal carcinoma.

Objectives: In malignant tumors, elevated infiltration of intratumoral CD8+ cytotoxic T cells predicts a beneficial prognosis, whereas high levels of CD15+ neutrophils in peritumor tissues indicate poor prognosis. It is unclear how SMAD4, which promotes favorable clinical outcomes and antitumor immunoregulation, along with CD8+ cytotoxic T cells and CD15+ neutrophils exert an influence on hypopharyngeal carcinoma (HPC). Materials and methods: Specimens were collected from 97 patients with HPC. Immunohistological analyses of SMAD4, CD8+ cytotoxic T cell and CD15+ neutrophil expression were performed. SMAD4 nuclear intensity was measured, meanwhile, CD8+ cytotoxic T cells and CD15+ neutrophils were counted under a microscope. The prognostic role of SMAD4 was determined using the log-rank test and univariate and multivariate analyses. The relationship among SMAD4, CD8+ cytotoxic T cells, and CD15+ neutrophils was estimated by Mann-Whitney U test. Results: High levels of SMAD4 were associated with favorable overall survival (OS) and disease-free survival (DFS) in HPC. Multivariate analysis suggested that SMAD4 is an independent predictor of OS and DFS. A high density of intratumoral CD8+ cytotoxic T cells and low accumulation of CD15+ neutrophils in the peritumor area were associated with longer OS and DFS. Furthermore, SMAD4 was linked to the levels of intratumoral CD8+ cytotoxic T cells and peritumoral CD15+ neutrophils. Patients with high SMAD4/high intratumoral CD8+ cytotoxic T cells or high SMAD4/low peritumoral CD15+ neutrophils showed the best prognosis. Conclusion: SMAD4, CD8+ cytotoxic T cell level, and CD15+ neutrophil level have prognostic value in HPC. SMAD4 is a promising prognostic marker reflecting immune response in HPC.

A Bayesian network model to predict neoplastic risk for patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

BACKGROUND: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. METHODS: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. RESULTS: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). CONCLUSION: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

Effectiveness and safety of camrelizumab in inoperable or advanced non-small cell lung cancer patients: a multicenter real-world retrospective observational study (CTONG2004-ADV).

Background: Camrelizumab plus chemotherapy have been approved as standards for the treatment of advanced non-small cell lung cancer (NSCLC) patients based on two phase III trials. However, clinical trial results may not be representative of the general population, as clinical trials often have specific inclusion and exclusion criteria. Our research aims to investigate the real-world effectiveness and safety of camrelizumab in inoperable or advanced NSCLC patients. Methods: This multicenter retrospective observational study included inoperable or advanced pathologically confirmed NSCLC patients who received at least one dose of camrelizumab at 22 hospitals. Clinical and follow-up data of camrelizumab were collected retrospectively from the medical records. The primary outcome was the objective response rate (ORR) and secondary outcomes were disease control rate (DCR), 6-month progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Multivariate logistic and Cox regression analyses were applied to identify potential predictive factors of ORR and PFS, respectively. Results: Between July 2019 and March 2021, 336 patients were included. Adenocarcinoma was seen in 58.4% and stage IV disease in 69.3%. Twenty-nine (8.6%) had liver metastasis at baseline. Most patients received camrelizumab in the first-line setting (74.1%) and in combination with chemotherapy (60.7%). The ORR was 40.2% [95% confidence interval (CI): 34.9-45.6%] and DCR was 85.1% (95% CI: 81.3-88.9%), while the 6-month PFS and OS rates were 73.0% (95% CI: 67.1-78.0%) and 93.1% (95% CI: 89.8-95.4%), respectively. In multivariate analyses, liver metastasis [odds ratio (OR), 0.324; 95% CI: 0.115-0.915; P=0.033] and increasing lines of camrelizumab treatment (vs. first line, second line: OR, 0.347; 95% CI: 0.162-0.741; P=0.006; ≥ third line: OR, 0.126; 95% CI: 0.043-0.367; P<0.001) were negatively associated, while a longer duration of camrelizumab treatment was positively associated with ORR and PFS. TRAEs were recorded in 164 (48.8%) patients, without new safety signal. Conclusions: We conducted a comprehensive overview of the effectiveness and safety profile of camrelizumab in a broader NSCLC population in real world NSCLC patients, and subgroup analysis indicated the presence of liver metastasis was associated with worse outcomes.

Efficacy and safety of PLDR-IMRT for the re-irradiation of recurrent NPC: A prospective, single-arm, multicenter trial.

Salvage treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) requires weighing the benefits of re-irradiation against increased risks of toxicity. Here, we evaluated the outcomes of patients treated with intensity-modulated-based pulsed low-dose-rate radiotherapy (PLDR-IMRT) to enhance the curative effect of salvage treatment and reduce RT-related SAEs. A prospective clinical trial was conducted from March 2018 to March 2020 at multiple institutions. NPC patients who experienced relapse after radical therapy were re-irradiated with a median dose of 60 Gy (50.4-70 Gy)/30 f (28-35 f) using PLDR-IMRT. Thirty-six NPC patients who underwent PLDR-IMRT for locoregional recurrence were identified. With a median follow-up of 26.2 months, the objective response rate (ORR) of the entire cohort was 91.6%. The estimated mPFS duration was 28 months (95% CI: 24.9-31.1), and the estimated mLRFS duration was 30.4 months (95% CI: 25.2-35.5). The overall survival (OS) rate for all patients was 80.6%, the progression-free survival (PFS) rate was 75% and the cancer-specific survival (CSS) rate was 88.9% at 1 year. The LRFS and DMFS rates were 88.9% and 91.7%, respectively, at 1 year. A combination of systematic therapies could provide survival benefits to patients who experience NPC relapse (p < 0.05), and a Karnofsky performance status (KPS) score of ≥90 was a favorable factor for local control (p < 0.05). The incidence of acute SAEs (grade 3+) from PLDR was 22.2%, and the incidence of chronic SAEs was 19.4% among all patients. PLDR-IMRT combined with systematic therapy can effectively treat patients with locoregionally recurrent nasopharyngeal carcinoma and causes fewer adverse events than the rates expected with IMRT.

Error detection using EPID-based 3D in vivo dose verification for lung stereotactic body radiotherapy.

PURPOSE: To investigate the error detectability limitations of an EPID-based 3D in vivo dosimetry verification system for lung stereotactic body radiation therapy (SBRT). METHODS: Thirty errors were intentionally introduced, consisting of dynamic and constant machine errors, to simulate the possible errors that may occur during delivery. The dynamic errors included errors in the output, gantry angle and MLC positions related to gantry inertial and gravitational effects, while the constant errors included errors in the collimator angle, jaw positions, central leaf positions, setup shift and thickness to simulate patient weight loss. These error plans were delivered to a CIRS phantom using the SBRT technique for lung cancer. Following irradiation of these error plans, the dose distribution was reconstructed using iViewDose™ and compared with the no error plan. RESULTS: All errors caused by the central leaf positions, dynamic MLC errors, Jaw inwards movements, setup shifts and patient anatomical changes were successfully detected. However, dynamic gantry angle and collimator angle errors were not detected in the lung case due to the rotation-symmetric target shape. The results showed that the γmean and γpassrate indicators can detect 13 (81.3%) and 14 (87.5%) of the 16 errors respectively without including the gantry angle error, collimator angle error and output error. CONCLUSIONS: In summary, iViewDose™ is an appropriate approach for detecting most types of clinical errors for lung SBRT. However, the phantom results also showed some detectability limitations of the system in terms of dynamic gantry angle and constant collimator angle errors.

Standard pancreatoduodenectomy versus extended pancreatoduodenectomy with modified retroperitoneal nerve resection in patients with pancreatic head cancer: a multicenter randomized controlled trial.

BACKGROUND: The extent of pancreatoduodenectomy for pancreatic head cancer remains controversial, and more high-level clinical evidence is needed. This study aimed to evaluate the outcome of extended pancreatoduodenectomy (EPD) with retroperitoneal nerve resection in pancreatic head cancer. METHODS: This multicenter randomized trial was performed at 6 Chinese high-volume hospitals that enrolled patients between October 3, 2012, and September 21, 2017. Four hundred patients with stage I or II pancreatic head cancer and without specific pancreatic cancer treatments (preoperative chemotherapy or chemoradiation) within three months were randomly assigned to undergo standard pancreatoduodenectomy (SPD) or EPD, with the latter followed by dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. The primary endpoint was overall survival (OS) by intention-to-treat (ITT). The secondary endpoints were disease-free survival (DFS), mortality, morbidity, and postoperative pain intensity. RESULTS: The R1 rate was slightly lower with EPD (8.46%) than with SPD (12.56%). The morbidity and mortality rates were similar between the two groups. The median OS was similar in the EPD and SPD groups by ITT in the whole study cohort (23.0 vs. 20.2 months, P = 0.100), while the median DFS was superior in the EPD group (16.1 vs. 13.2 months, P = 0.031). Patients with preoperative CA19-9 < 200.0 U/mL had significantly improved OS and DFS with EPD (EPD vs. SPD, 30.8 vs. 20.9 months, P = 0.009; 23.4 vs. 13.5 months, P < 0.001). The EPD group exhibited significantly lower locoregional (16.48% vs. 35.20%, P < 0.001) and mesenteric LN recurrence rates (3.98% vs. 10.06%, P = 0.022). The EPD group exhibited less back pain 6 months postoperation than the SPD group. CONCLUSIONS: EPD for pancreatic head cancer did not significantly improve OS, but patients with EPD treatment had significantly improved DFS. In the subgroup analysis, improvements in both OS and DFS in the EPD arm were observed in patients with preoperative CA19-9 < 200.0 U/mL. EPD could be used as an effective surgical procedure for patients with pancreatic head cancer, especially those with preoperative CA19-9 < 200.0 U/mL.

Evaluation of chemotherapy and radiotherapy in the adjuvant management of uterine carcinosarcoma: a population-based analysis.

PURPOSE: To evaluate the effects of adjuvant chemotherapy (CT) and radiotherapy (RT) on the survival of uterine carcinosarcoma (UCS) patients. METHODS: We analyzed 3207 patients with uterine carcinosarcoma without distant metastasis after surgery from 2004 to 2015 by utilizing data from the Surveillance, Epidemiology, and End Results database. Generally, cancer-specific survival (CSS) and overall survival (OS) outcomes were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Further subgroup survival analysis was performed for those receiving RT and chemoradiotherapy (CRT). RESULTS: In general, both univariate and multivariate analyses showed that age, race, marital status, stage, lymph node metastasis, lymphadenectomy (LND), RT, and chemotherapy (CT) were associated with improved CSS and OS (P < 0.05). Further subgroup analysis showed that CRT exhibited a survival advantage over RT or CT alone in different groups. Various RT modalities, including brachytherapy (BT), external radiotherapy (EBRT), and EBRT + BT, were correlated with improved survival for patients aged 60-69 years with stage III-IV disease and lymph node metastasis. Patients with stage I-II disease aged > 70 years seemed to gain survival benefits from brachytherapy (BT) alone. BT with or without external radiotherapy was associated with improved survival for those who did not undergo lymphadenectomy. CONCLUSION: For UCS without distant metastasis after surgery, CRT should be considered. Regarding RT, BT alone is efficient in improving survival, especially for patients with stage I-II disease aged > 70 years old. EBRT alone does not show results in survival improvement for patients who did not undergo LND and those with lymph node metastasis. However, considering the limitation of SEER database, further studies with more large sample size and strict study design are needed to confirm it.

A Bayesian network prediction model for gallbladder polyps with malignant potential based on preoperative ultrasound.

BACKGROUND: It is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8-15 mm based on preoperative ultrasound. METHODS: The independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables. RESULTS: Independent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0-0.2), [0.2-0.5), [0.5-0.8) and [0.8-1] according to the total points of [- 337, - 234], [- 197, - 145], [- 123, - 108], and [- 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively. CONCLUSION: A BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8-15 mm undergoing cholecystectomy based on preoperative ultrasound.

Contouring the accessory parotid gland and major parotid glands as a single organ at risk during nasopharyngeal carcinoma radiotherapy.

Background and purpose: No research currently exists on the role of the accessory parotid gland (APG) in nasopharyngeal carcinoma (NPC). We thereby aimed to assess the effects of APG on the dosimetry of the parotid glands (PGs) during NPC radiotherapy and evaluate its predictive value for late xerostomia. Material and methods: The clinical data of 32 NPC patients with radiological evidence of the APG treated at Sun Yat-sen Memorial Hospital between November 2020 and February 2021 were retrospectively reviewed. Clinically approved treatment plans consisted of only the PGs as an organ at risk (OAR) (Plan1), while Plan2 was designed by considering the APG as a single organ at risk (OAR). The APG on Plan1 was delineated, and dose-volume parameters of the PGs alone (PG-only) and of the combined structure (PG+APG) were analyzed in both plans. The association of such dosimetric parameters in Plan1 with xerostomia at 6-9 months post-radiotherapy was further explored. Results: Fifty APGs were found, with a mean volume of 3.3 ± 0.2 ml. Significant differences were found in all dosimetric parameters between Plan1 and Plan2. The mean dose and percentage of OAR volumes receiving more than 30 Gy significantly reduced in Plan1 itself (PG-only vs. PG+APG, 39.55 ± 0.83 Gy vs. 37.71 ± 0.75 Gy, and 62.00 ± 2.00% vs. 57.41 ± 1.56%, respectively; p < 001) and reduced further in Plan2 (PG+APG, 36.40 ± 0.74 Gy, and 55.54 ± 1.61%, respectively; p < 0.001). Three additional patients met the dose constraint in Plan1, which increased to seven in Plan2. With APG included, the predictive power of the dosimetric parameters for xerostomia tended to improve, although no significant differences were observed. Conclusion: APG is anatomically similar to the PGs. Our findings suggest the potential benefits of treating the APG and PGs as a single OAR during radiotherapy (RT) of NPC by improving PG sparing.

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization.

BACKGROUND: Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. METHODS: Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-ß and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. RESULTS: Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). CONCLUSIONS: In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.

2,6-Difluorobenzamide derivatives as store-operated calcium channel (SOC) inhibitors.

The Ca2+ entry from store-operated Ca2+ channel (SOC) is involved in regulating colorectal cancer progression, such as cell migration. SOC activation is due to STIM1 translocation and interaction with Orai1 upon Ca2+ depletion in the ER. Numerous SOC inhibitors, like 2-APB, have been developed and demonstrated their inhibition effects in the preclinical stage. However, most currently used SOC inhibitors have higher cytotoxicity or opposite effects at different doses, and the drugs to target SOC in the clinic are lacking. In this study, a total of 13 difluorobenzamide compounds had been synthesized and examined the inhibitory effects on SOC with Ca2+ imaging and wound-healing migration assay. Among them, 2,6-Difluoro-N-(5-(4-fluorophenyl)pyridine-2-yl)benzamide (MPT0M004, 8a) demonstrated a prominent inhibitory ability on SOC. Furthermore, the cell proliferation assay results showed that MPT0M004 (8a) had lower cytotoxicity than 2-APB, the reference compound. In the pharmacokinetic study, MPT0M004 (8a) has a long half-life (T1/2 = 24 h) and lower daily dose administered intravenously with an oral bioavailability (F = 34%). Therefore, MPT0M004 (8a) has the potential to be a lead compound as a SOC inhibitor and further develop into a potential drug to treat colorectal cancer.

Prevalence and risk factors analysis for low back pain among occupational groups in key industries of China.

BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.

Plasma Circulating Tumor Epstein-Barr Virus for the Surveillance of Cancer Progression in Bone-Only Metastatic Nasopharyngeal Carcinoma.

Background: Plasma Epstein-Barr virus DNA (EBV-DNA) is a sensitive and specific biomarker for nasopharyngeal carcinoma (NPC). We investigated whether longitudinal monitoring of EBV-DNA could accurately detect clinical disease progression in NPC patients with bone-only metastases. Methods: In this retrospective study, a total of 105 patients with bone-only metastatic NPC who were treated with platinum-based first-line chemotherapy were enrolled. Undetectable EBV-DNA after first-line chemotherapy was defined as a biochemical complete response (BCR). The correlation of the EBV-DNA dynamic status with overall survival (OS) and progression-free survival (PFS) was determined by Cox regression. The correlation between non-normalized EBV-DNA period and PFS period was determined. Results: After a median follow-up time of 53.4 months [Interquartile range (IQR): 42.8-80.6], 64 patients had disease progression. Thirty-nine of 105 patients (37.1%) had a BCR at all follow-up time points, and none of these 39 patients had disease progression, corresponding to a negative predictive value (NPV) of 100%. Sixty-six patients had a detectable EBV-DNA during surveillance, with 64 diagnosed as disease progression at the last follow-up, for a positive predictive value (PPV) of 97.0%. Actuarial 3-year OS rates were 45.0% for patients with detectable EBV-DNA during posttreatment surveillance and 100% for patients with undetectable EBV-DNA. Lastly, median lead time between non-normalized EBV-DNA and clinically proven progression was 5.87 ± 0.67 months. Conclusions: Taken together, EBV-DNA provided predictive value for the bone-only metastatic NPC patients. The results should be validated in prospective randomized studies.